Figure 1.

Ontogeny of tissue-resident lymphocytes. All lymphocytes develop from the common lymphoid progenitor (CLP). In the bone marrow, an early innate lymphoid progenitor (EILp) can give rise to natural killer (NK) cells and innate lymphoid cells (ILCs). Whereas, the identity of an NK-restricted progenitor (NKp) remains unknown, a committed innate lymphoid cell progenitor (ILCp), which can give rise to all helper ILCs (ILChs), but not NK cells has been described. Less understood, ILCs with cytotoxic potential, or killer ILCs (ILCk) may arise from a hypothetical killer ILC progenitor (ILCkp) that have lost ILCh and NK potential. While ILCs are inherently tissue-resident, NK cells recirculate. Whether NK cells can acquire tissue-resident features remains unknown. Thus, the term tissue-resident NK (trNK) cells is better kept until such a possibility can be unequivocally ruled out. Beside innate lymphocytes, CLP also gives rise to T lineage-committed progenitors that complete their differentiation in the thymus. The vast majority of TCRαβ-expressing T cells undergo a double positive (DP) stage, during which MHC-based selection takes place. DP thymocytes bearing strongly self-reactive TCRs develop into unconventional intraepithelial lymphocyte (IEL) and natural killer T (NKT) cell lineages through agonist selection, while those with weakly self-reactive TCRs are diverted into single positive (SP) thymocytes, which subsequently give rise to conventional T (conv. T) cells. Whereas, IELs and NKT cells are naturally tissue-resident, conventional T cells recirculate but can become tissue-resident (T_RM) upon activation.